The β-globin nuclear compartment in development and erythroid differentiation
Abstract
Efficient transcription of genes requires a high local concentration of the relevant trans-acting factors. Nuclear compartmentalization can provide an effective means to locally increase the concentration of rapidly moving trans-acting factors; this may be achieved by spatial clustering of chromatin-associated binding sites for such factors. Here we analyze the structure of an erythroid-specific spatial cluster of cis-regulatory elements and active beta-globin genes, the active chromatin hub (ACH; ref. 6), at different stages of development and in erythroid progenitors. We show, in mice and humans, that a core ACH is developmentally conserved and consists of the hypersensitive sites (HS1-HS6) of the locus control region (LCR), the upstream 5' HS-60/-62 and downstream 3' HS1. Globin genes switch their interaction with this cluster during development, correlating with the switch in their transcriptional activity. In mouse erythroid progenitors that are committed to but do not yet express beta-globin, only the interactions between 5' HS-60/-62, 3' HS1 and hypersensitive sites at the 5' side of the LCR are stably present. After induction of differentiation, these sites cluster with the rest of the LCR and the gene that is activated. We conclude that during erythroid differentiation, cis-regulatory DNA elements create a developmentally conserved nuclear compartment dedicated to RNA polymerase II transcription of beta-globin genes.
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Further 3C experiments over a developmental time course revealed that the LCR interacts with different β-globin genes depending on the stage of erythroid cell development.
“Further 3C experiments over a developmental time course revealed that the LCR interacts with different β-globin genes depending on the stage of erythroid cell development [268].”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [268]
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- Authors
- Palstra, R.-J., Tolhuis, B., Splinter, E., Nijmeijer, R., Grosveld, F., & de Laat, W.
- Affiliations
- Erasmus MC (NL)
- Venue
- Nature Genetics
- Published
- 2003-09-21
- Volume
- 35
- Issue
- 2
- Pages
- 190-194
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1971615450
- Cited by
- 559
- References
- 2
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 7 · 2023: 14 · 2022: 23 · 2021: 28 · 2020: 22 · 2019: 15 · 2018: 24 · 2017: 24 · 2016: 26 · 2015: 29 · 2014: 16 · 2013: 33 · 2012: 39
- FWCI
- 8.41
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Keywords
- beta-globin gene, nuclear compartmentalization, erythroid differentiation, erythroid progenitor cells, locus control region, hypersensitive sites, cis-regulatory elements, RNA polymerase II transcription, developmental gene regulation
- MeSH terms
- Animals, Brain, Cell Differentiation, Cell Nucleus, Chromatin, Chromosome Mapping, Globins, Hematopoietic Stem Cells, Humans, Transcription, Genetic, Gene Expression Regulation, Developmental, Protein Transport, Mice
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